Immunopathological basis of lymphocytic choriomeningitis virus-induced chorioretinitis and keratitis.
The infection of humans with the rodent-borne lymphocytic choriomeningitis virus (LCMV) can lead to central nervous system disease in adults or severe neurological disease with hydrocephalus and chorioretinitis in children infected congenitally. Although LCMV-induced meningitis and encephalitis have been studied extensively, the immunopathological mechanisms underlying LCMV infection-associated ocular disease remain elusive. We report here that the intraocular administration of the neurotropic LCMV strain Armstrong (Arm) elicited pronounced chorioretinitis and keratitis and that infection with the more viscerotropic strains WE and Docile precipitated less severe immunopathological ocular disease. Time course analyses revealed that LCMV Arm infection of the uvea and neuroretina led to monophasic chorioretinitis which peaked between days 7 and 12 after infection. Analyses of T-cell-deficient mouse strains showed that LCMV-mediated ocular disease was strictly dependent on the presence of virus-specific CD8(+) T cells and that the contribution of CD4(+) T cells was negligible. Whereas the topical application of immunosuppressive agents did not prevent the development of chorioretinitis, passive immunization with hyperimmune sera partially prevented retinal and corneal damage. Likewise, mice displaying preexisting LCMV-specific T-cell responses were protected against LCMV-induced ocular disease. Thus, antibody- and/or T-cell-based vaccination protocols could be employed as preventive strategies against LCMV-mediated chorioretinitis.
Zinkernagel
Martin S
MS
Research Department, Kantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland.
Bolinger
Beatrice
B
Krebs
Philippe
P
Onder
Lucas
L
Miller
Simone
S
Ludewig
Burkhard
B
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002825:Chorioretinitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007114:Immunization; D007116:Immunization, Passive; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007634:Keratitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000914:Antibodies, Viral; D007166:Immunosuppressive Agents